1921
Volume 84, Issue 2_Suppl
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

circumsporozoite (CS) protein is a leading malaria vaccine candidate. We describe the characterization of specific immune responses induced in 21 malaria-naive volunteers vaccinated with long synthetic peptides derived from the CS protein formulated in Montanide ISA 720. Both antibody- and cell-mediated immune responses were analyzed. Antibodies were predominantly of IgG1 and IgG3 isotypes, recognized parasite proteins on the immunofluorescent antibody test, and partially blocked sporozoite invasion of hepatoma cell lines . Peripheral blood mononuclear cells from most volunteers (94%) showed IFN-γ production upon stimulation with both long signal peptide and short peptides containing CD8+ T-cell epitopes. The relatively limited sample size did not allow conclusions about HLA associations with the immune responses observed. In summary, the inherent safety and tolerability together with strong antibody responses, invasion blocking activity, and the IFN-γ production induced by these vaccine candidates warrants further testing in a phase II clinical trial.

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References

  1. Mendis K, Sina BJ, Marchesini P, Carter R, , 2001. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 64: 97106.
  2. Clyde DF, , 1990. Immunity to falciparum and vivax malaria induced by irradiated sporozoites: a review of the University of Maryland studies, 1971–75. Bull World Health Organ 68 (Suppl): 912.
  3. Herrington D, Davis J, Nardin E, Beier M, Cortese J, Eddy H, Losonsky G, Hollingdale M, Sztein M, Levine M, Nussenzweig RS, Clyde D, Edelman R, , 1991. Successful immunization of humans with irradiated malaria sporozoites: humoral and cellular responses of the protected individuals. Am J Trop Med Hyg 45: 539547.
  4. Hoffman SL, Goh LM, Luke TC, Schneider I, Le TP, Doolan DL, Sacci J, de la Vega P, Dowler M, Paul C, Gordon DM, Stoute JA, Church LW, Sedegah M, Heppner DG, Ballou WR, Richie TL, , 2002. Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites. J Infect Dis 185: 11551164.[Crossref]
  5. Hollingdale MR, Nardin EH, Tharavanij S, Schwartz AL, Nussenzweig RS, , 1984. Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies. J Immunol 132: 909913.
  6. Herrera S, Corradin G, Arévalo-Herrera M, , 2007. An update on the search for a Plasmodium vivax vaccine. Trends Parasitol 23: 122128.[Crossref]
  7. Sharma S, Pathak S, , 2008. Malaria vaccine: a current perspective. J Vector Borne Dis 45: 120.
  8. Nardin E, Zavala F, Nussenzweig V, Nussenzweig RS, , 1999. Pre-erythrocytic malaria vaccine: mechanisms of protective immunity and human vaccine trials. Parassitologia 41: 397402.
  9. Schofield L, Villaquiran J, Ferreira A, Schellekens H, Nussenzweig R, Nussenzweig V, , 1987. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature 330: 664666.[Crossref]
  10. Doolan DL, Martinez-Alier N, , 2006. Immune response to pre-erythrocytic stages of malaria parasites. Curr Mol Med 6: 169185.[Crossref]
  11. Mellouk S, Green SJ, Nacy CA, Hoffman SL, , 1991. IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. J Immunol 146: 39713976.
  12. Mellouk S, Maheshwari RK, Rhodes-Feuillette A, Beaudoin RL, Berbiguier N, Matile H, Miltgen F, Landau I, Pied S, Chigot JP, Friedman RM, Mazier D, , 1987. Inhibitory activity of interferons and interleukin 1 on the development of Plasmodium falciparum in human hepatocyte cultures. J Immunol 139: 41924195.
  13. Egan JE, Weber JL, Ballou WR, Hollingdale MR, Majarian WR, Gordon DM, Maloy WL, Hoffman SL, Wirtz RA, Schneider I, Woollett GR, Young JF, Hockmeyer WT, , 1987. Efficacy of murine malaria sporozoite vaccines: implications for human vaccine development. Science 236: 453456.[Crossref]
  14. Graves P, Gelband H, , 2003. Vaccines for preventing malaria. Cochrane Database Syst Rev CD000129.
  15. Moorthy V, Smith PG, Kieny MP, , 2009. A vaccine against malaria: a substantial step forward. Lancet 373: 14111412.[Crossref]
  16. Stoute JA, Kester KE, Krzych U, Wellde BT, Hall T, White K, Glenn G, Ockenhouse CF, Garcon N, Schwenk R, Lanar DE, Sun P, Momin P, Wirtz RA, Golenda C, Slaoui M, Wortmann G, Holland C, Dowler M, Cohen J, Ballou WR, , 1998. Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine. J Infect Dis 178: 11391144.[Crossref]
  17. Bojang KA, Milligan PJ, Pinder M, Vigneron L, Alloueche A, Kester KE, Ballou WR, Conway DJ, Reece WH, Gothard P, Yamuah L, Delchambre M, Voss G, Greenwood BM, Hill A, McAdam KP, Tornieporth N, Cohen JD, Doherty T, , 2001. Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet 358: 19271934.[Crossref]
  18. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, Mandomando I, Spiessens B, Guinovart C, Espasa M, Bassat Q, Aide P, Ofori-Anyinam O, Navia MM, Corachan S, Ceuppens M, Dubois MC, Demoitie MA, Dubovsky F, Menendez C, Tornieporth N, Ballou WR, Thompson R, Cohen J, , 2004. Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364: 14111420.[Crossref]
  19. Aponte JJ, Aide P, Renom M, Mandomando I, Bassat Q, Sacarlal J, Manaca MN, Lafuente S, Barbosa A, Leach A, Lievens M, Vekemans J, Sigauque B, Dubois MC, Demoitie MA, Sillman M, Savarese B, McNeil JG, Macete E, Ballou WR, Cohen J, Alonso PL, , 2007. Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. Lancet 370: 15431551.[Crossref]
  20. Moorthy VS, Reed Z, Smith PG, , 2009. Clinical trials to estimate the efficacy of preventive interventions against malaria in paediatric populations: a methodological review. Malar J 8: 23.[Crossref]
  21. Macete E, Aponte JJ, Guinovart C, Sacarlal J, Ofori-Anyinam O, Mandomando I, Espasa M, Bevilacqua C, Leach A, Dubois MC, Heppner DG, Tello L, Milman J, Cohen J, Dubovsky F, Tornieporth N, Thompson R, Alonso PL, , 2007. Safety and immunogenicity of the RTS,S/AS02A candidate malaria vaccine in children aged 1–4 in Mozambique. Trop Med Int Health 12: 3746.
  22. Macete EV, Sacarlal J, Aponte JJ, Leach A, Navia MM, Milman J, Guinovart C, Mandomando I, Lopez-Pua Y, Lievens M, Owusu-Ofori A, Dubois MC, Cahill CP, Koutsoukos M, Sillman M, Thompson R, Dubovsky F, Ballou WR, Cohen J, Alonso PL, , 2007. Evaluation of two formulations of adjuvanted RTS, S malaria vaccine in children aged 3 to 5 years living in a malaria-endemic region of Mozambique: a Phase I/IIb randomized double-blind bridging trial. Trials 8: 11.[Crossref]
  23. Bojang KA, Olodude F, Pinder M, Ofori-Anyinam O, Vigneron L, Fitzpatrick S, Njie F, Kassanga A, Leach A, Milman J, Rabinovich R, McAdam KP, Kester KE, Heppner DG, Cohen JD, Tornieporth N, Milligan PJ, , 2005. Safety and immunogenicty of RTS,S/AS02A candidate malaria vaccine in Gambian children. Vaccine 23: 41484157.[Crossref]
  24. Sun P, Schwenk R, White K, Stoute JA, Cohen J, Ballou WR, Voss G, Kester KE, Heppner DG, Krzych U, , 2003. Protective immunity induced with malaria vaccine, RTS,S, is linked to Plasmodium falciparum circumsporozoite protein-specific CD4+ and CD8+ T cells producing IFN-gamma. J Immunol 171: 69616967.[Crossref]
  25. Herrera S, Bonelo A, Perlaza BL, Fernandez OL, Victoria L, Lenis AM, Soto L, Hurtado H, Acuna LM, Velez JD, Palacios R, Chen-Mok M, Corradin G, Arévalo-Herrera M, , 2005. Safety and elicitation of humoral and cellular responses in colombian malaria-naive volunteers by a Plasmodium vivax circumsporozoite protein-derived synthetic vaccine. Am J Trop Med Hyg 73: 39.
  26. Yadava A, Sattabongkot J, Washington MA, Ware LA, Majam V, Zheng H, Kumar S, Ockenhouse CF, , 2007. A novel chimeric Plasmodium vivax circumsporozoite protein induces biologically functional antibodies that recognize both VK210 and VK247 sporozoites. Infect Immun 75: 11771185.[Crossref]
  27. Arévalo-Herrera M, Herrera S, , 2001. Plasmodium vivax malaria vaccine development. Mol Immunol 38: 443455.[Crossref]
  28. Arévalo-Herrera M, Roggero MA, Gonzalez JM, Vergara J, Corradin G, Lopez JA, Herrera S, , 1998. Mapping and comparison of the B-cell epitopes recognized on the Plasmodium vivax circumsporozoite protein by immune Colombians and immunized Aotus monkeys. Ann Trop Med Parasitol 92: 539551.[Crossref]
  29. Herrera S, Bonelo A, Perlaza BL, Valencia AZ, Cifuentes C, Hurtado S, Quintero G, Lopez JA, Corradin G, Arévalo-Herrera M, , 2004. Use of long synthetic peptides to study the antigenicity and immunogenicity of the Plasmodium vivax circumsporozoite protein. Int J Parasitol 34: 15351546.[Crossref]
  30. Arévalo-Herrera M, Valencia AZ, Vergara J, Bonelo A, Fleischhauer K, Gonzalez JM, Restrepo JC, Lopez JA, Valmori D, Corradin G, Herrera S, , 2002. Identification of HLA-A2 restricted CD8(+) T-lymphocyte responses to Plasmodium vivax circumsporozoite protein in individuals naturally exposed to malaria. Parasite Immunol 24: 161169.[Crossref]
  31. Atherton E, Logan CJ, Sheppard RC, , 1981. Procedures for solid-phase synthesis using N-fluorenylmethoxycarbonylamino-acids on polyamide supports. Synthesis of substance P and of acyl carrier protein 65–74 decapeptide. J Chem Soc, Perkin Trans 1 538546.[Crossref]
  32. Roggero MA, Servis C, Corradin G, , 1997. A simple and rapid procedure for the purification of synthetic polypeptides by a combination of affinity chromatography and methionine chemistry. FEBS Lett 408: 285288.[Crossref]
  33. Bouharoun-Tayoun H, Druilhe P, , 1992. Plasmodium falciparum malaria: evidence for an isotype imbalance which may be responsible for delayed acquisition of protective immunity. Infect Immun 60: 14731481.
  34. Druilhe P, Tall A, Sokhna C, , 2005. Worms can worsen malaria: towards a new means to roll back malaria? Trends Parasitol 21: 359362.[Crossref]
  35. Oeuvray C, Theisen M, Rogier C, Trape JF, Jepsen S, Druilhe P, , 2000. Cytophilic immunoglobulin responses to Plasmodium falciparum glutamate-rich protein are correlated with protection against clinical malaria in Dielmo, Senegal. Infect Immun 68: 26172620.[Crossref]
  36. Soe S, Theisen M, Roussilhon C, Aye KS, Druilhe P, , 2004. Association between protection against clinical malaria and antibodies to merozoite surface antigens in an area of hyperendemicity in Myanmar: complementarity between responses to merozoite surface protein 3 and the 220-kilodalton glutamate-rich protein. Infect Immun 72: 247252.[Crossref]
  37. Hurtado S, Salas ML, Romero JF, Zapata JC, Ortiz H, Arévalo-Herrera M, Herrera S, , 1997. Regular production of infective sporozoites of Plasmodium falciparum and P. vivax in laboratory-bred Anopheles albimanus . Ann Trop Med Parasitol 91: 4960.[Crossref]
  38. Gonzalez JM, Hurtado S, Arévalo-Herrera M, Herrera S, , 2001. Variants of the Plasmodium vivax circumsporozoite protein (VK210 and VK247) in Colombian isolates. Mem Inst Oswaldo Cruz 96: 709712.[Crossref]
  39. Renia L, Vigario AM, Belnoue E, , 2002. Inhibition of sporozoite invasion. The double-staining assay. Methods Mol Med 72: 507516.
  40. Nasiri H, Forouzandeh M, Rasaee MJ, Rahbarizadeh F, , 2005. Modified salting-out method: high-yield, high-quality genomic DNA extraction from whole blood using laundry detergent. J Clin Lab Anal 19: 229232.[Crossref]
  41. Herrera S, De Plata C, Gonzalez M, Perlaza BL, Bettens F, Corradin G, Arévalo-Herrera M, , 1997. Antigenicity and immunogenicity of multiple antigen peptides (MAP) containing P. vivax CS epitopes in Aotus monkeys. Parasite Immunol 19: 161170.[Crossref]
  42. Bongfen SE, Ntsama PM, Offner S, Smith T, Felger I, Tanner M, Alonso P, Nebie I, Romero JF, Silvie O, Torgler R, Corradin G, , 2009. The N-terminal domain of Plasmodium falciparum circumsporozoite protein represents a target of protective immunity. Vaccine 27: 328335.[Crossref]
  43. Ying P, Shakibaei M, Patankar MS, Clavijo P, Beavis RC, Clark GF, Frevert U, , 1997. The malaria circumsporozoite protein: interaction of the conserved regions I and II-plus with heparin-like oligosaccharides in heparan sulfate. Exp Parasitol 85: 168182.[Crossref]
  44. Coppi A, Pinzon-Ortiz C, Hutter C, Sinnis P, , 2005. The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion. J Exp Med 201: 2733.[Crossref]
  45. Ancsin JB, Kisilevsky R, , 2004. A binding site for highly sulfated heparan sulfate is identified in the N terminus of the circumsporozoite protein: significance for malarial sporozoite attachment to hepatocytes. J Biol Chem 279: 2182421832.[Crossref]
  46. Fries LF, Gordon DM, Schneider I, Beier JC, Long GW, Gross M, Que JU, Cryz SJ, Sadoff JC, , 1992. Safety, immunogenicity, and efficacy of a Plasmodium falciparum vaccine comprising a circumsporozoite protein repeat region peptide conjugated to Pseudomonas aeruginosa toxin A. Infect Immun 60: 18341839.
  47. Oliveira GA, Wetzel K, Calvo-Calle JM, Nussenzweig R, Schmidt A, Birkett A, Dubovsky F, Tierney E, Gleiter CH, Boehmer G, Luty AJ, Ramharter M, Thornton GB, Kremsner PG, Nardin EH, , 2005. Safety and enhanced immunogenicity of a hepatitis B core particle Plasmodium falciparum malaria vaccine formulated in adjuvant Montanide ISA 720 in a phase I trial. Infect Immun 73: 35873597.[Crossref]
  48. Druilhe P, Perignon JL, , 1994. Mechanisms of defense against P. falciparum asexual blood stages in humans. Immunol Lett 41: 115120.[Crossref]
  49. Thomas BE, Manocha M, Haq W, Adak T, Pillai CR, Rao DN, , 2001. Modulation of the humoral response to repeat and non-repeat sequences of the circumsporozoite protein of Plasmodium vivax using novel adjuvant and delivery systems. Ann Trop Med Parasitol 95: 451472.[Crossref]
  50. Fruci D, Rovero P, Falasca G, Chersi A, Sorrentino R, Butler R, Tanigaki N, Tosi R, , 1993. Anchor residue motifs of HLA class-I-binding peptides analyzed by the direct binding of synthetic peptides to HLA class I alpha chains. Hum Immunol 38: 187192.[Crossref]
  51. Tanigaki N, Fruci D, Chersi A, Falasca G, Tosi R, Butler RH, , 1994. HLA-A2-binding peptides cross-react not only within the A2 subgroup but also with other HLA-A-locus allelic products. Hum Immunol 39: 155162.[Crossref]
  52. Tippawangkosol P, Duangchanda T, Ubalee R, Ruengweerayut R, Hirayama K, Na-Bangchang K, , 2009. Identification of HLA-A24 restricted pre-erythrocytic stage specific T-cell epitopes using Plasmodium falciparum synthetic peptides: a preliminary study. Southeast Asian J Trop Med Public Health 40: 1017.
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  • Received : 31 Aug 2009
  • Accepted : 27 Feb 2010

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